The alternate iron transport pathway: mobilferrin and integrin in reticulocytes

Iron transport in reticulocytes is known to occur via the well-described transferrin-receptor–endosome pathway. An alternative pathway for iron transport independent of transferrin has been postulated in reticulocytes and other cells. Transport of iron into reticulocytes from ferric citrate solutions was shown to be saturable and independent of transferrin. During transport of iron from ferric citrate, both cell surface integrins, and a soluble protein, mobilferrin, were labelled. This demonstrated that the reticulocyte transferrin independent pathway for iron transport involved integrins and mobilferrin similar to intestinal absorptive cells. This pathway would be expected to transport iron into cells under conditions of iron overload and was capable of providing iron for haemoglobin synthesis. Mobilferrin was also radiolabelled when radioiron labelled transferrin was incubated with reticulocytes and this occurred with a different time course than was observed following reticulocyte exposure to radiolabelled ferric citrate. This suggested that mobilferrin may serve as an intermediary in both pathways.     

Precision Medicine Approaches to Vascular Disease: JACC Focus Seminar 2/5

In this second of a 5-part Focus Seminar series, we focus on precision medicine in the context of vascular disease. The most common vascular disease worldwide is atherosclerosis, which is the primary cause of coronary artery disease, peripheral vascular disease, and a large proportion of strokes and other disorders. Atherosclerosis is a complex genetic disease that likely involves many hundreds to thousands of single nucleotide polymorphisms, each with a relatively modest effect for causing disease. Conversely, although less prevalent, there are many vascular disorders that typically involve only a single genetic change, but these changes can often have a profound effect that is sufficient to cause disease. These are termed “Mendelian vascular diseases,” which include Marfan and Loeys-Dietz syndromes. Given the very different genetic basis of atherosclerosis versus Mendelian vascular diseases, this article was divided into 2 parts to cover the most promising precision medicine approaches for these disease types.     

Long-term survival after post-hepatectomy liver failure for colorectal liver metastases

Background

While post-hepatectomy liver failure (PHLF) accurately predicts short-term mortality, its role in prognosticating long-term overall survival (OS) remains unclear.